The main objective of the proposed research is to investigate the mechanism of the interaction of fibrinogen and polymerizing fibrin with blood cells, platelets, erythrocytes and leukocytes and to relate these interactions to the pathogenesis of thrombosis. The term polymerizing fibrin is used to describe intermediate products of the fibrinogen-fibrin conversion. Polymerizing fibrin contains changing proportions of fibrinogen, of free and complexed fibrin monomer and fibrin oligomers of various molecular weight. In addition to this heterogeneous mixture we also intend to investigate the interaction of blood cells with isolated and better defined fibrinogen-fibrin monomer complexes. More specifically, the project has the following long-term objectives: a) Study of the binding kinetics of fibrinogen and fibrinogen-fibrin monomer complexes to platelets; b) Identification and characterization of the component(s) of the platelet membranes which interact with fibrinogen and with fibrin monomers or polymerizing fibrin; c) Study of the interaction between fibrinogen or polymerizing fibrin and red blood cells and PMN leukocytes; d) Distribution of fibrinogen and fibrin binding sites on the cell surface by means of electronmicroscopy; e) Interrelationship between binding of fibrinogen and fibrin monomers to platelets and platelet aggregation and platelet release reaction; f) Interrelationship between fibrinogen structure and its platelet or red cell aggregation promoting activities; g) Interaction between polymerizing fibrin and cells in vivo; and h) Study of some clinical and pathological aspects of the interaction of blood cells with fibrinogen and fibrin.